Association of HBV variability and Aflatoxin B1 exposure on liver disease in West Africa

Abstract

Hepatitis B virus (HBV) infection is one of the main causes of hepatocellular carcinoma (HCC) globally with 50% of the HCC cases in Africa associated with this infectious agent. There is considerable evidence that HBV genetic variants and genotypes have different molecular and clinical impacts and certain viral proteins are oncogenic. Aflatoxin B1 (AFB1) is also a well-known carcinogenic agent, highly endemic in this region. Yet these factors remain poorly documented in West Africa. The objective was to assess the carriage of HBV variants, the distribution of different genotypes and the exposure to AFB1 in respect to the clinical status of HBV-infected patients in the Gambia. In our case-control study nested within the PROLIFICA programme, consecutive treatment-naïve, hepatitis B surface antigen (HBsAg) chronic carriers with detectable viral load were recruited; 211 controls with no significant liver disease (74% males, median viral load 2.7 (IQR 2.2-3.3) log10 IU/ml, HBeAg-positive 9%, genotype E 89%) and 91 cases composed of 56 cirrhotic patients (84% males, median viral load 4.0 (IQR 2.3-5.9) log10 IU/ml, HBeAg-positive 31%, genotype E 86%) and 35 HCC cases (71% males, median viral load 5.2 (IQR 3.2-6.3), HBeAg-positive (40%), genotype E 57%). Multiple surface gene variants were more frequently observed in cases (43% and 57% in cirrhotic and HCC cases, respectively) than controls (25%, p<0.001), with a PreS2 deletion between nucleotides 38-55 (PreS2∆38-55) being the main variant. In multivariable analysis HBeAg-seropositivity, low HBsAg levels and HDV seropositivity were significantly associated with cirrhosis and HCC, whilst older age, higher viral load, genotype A, PreS2∆38-55, and AFB1 exposure were associated only with HCC. There was a multiplicative joint effect of PreS2∆38-55 variants with HBeAg-seropositivity (OR 43.1 (10.4-177.7)), high viral load >2,000 IU/ml (OR 22.7 (8.0-64.9)), low HBsAg levels <10,000 IU/ml